Preparation of 3-substituted 2-hydroxyquinoxalines by reaction of 0-arylenediamines with trihalovinyl epoxides

ABSTRACT

Described are a general process for making 3-substituted 2hydroxyquinoxalines by reaction of o-arylenediamines with trihalovinyl epoxides and certain novel 2-hydroxy-3perfluoroalkylquinoxalines made by the process.

United States Patent Nottke Dec. 23, 1975 PREPARATION OF 3-SUBS'IITUTED Z-HYDROXYQUINOXALINES BY [56] References Cited REACTION OF O-ARYLENEDIAMINES WITH TRIHALOVINYL EPOXIDES inventor: James E. Nottke, Wilmington, Del.

Assignee: E. l. Du Pont de Nemours and Company, Wilmington, Del.

Filed: Aug. 27, 1913 Appl. No.: 391,524

Related us. Application Data Division of Ser. No. 158,520, June 30, l97l.

abandoned.

OTHER PUBLICATIONS Tkaczynski, Chemical Abstracts," 1966, 64, l7594d. Simpson, The Chemistry of Heterocyclic Compounds," l953, pp. 1020-102l, 235-240.

Primary Examiner-Donald G. Daus Assistant Examiner-David E. Wheeler [57] ABSTRACT Described are a general process for making 3- substituted Z-hydroxyquinoxalines by reaction of oarylenediamines with trihalovinyl epoxides and certain novel 2-hydroxy-3-perfluoroaikylquinoxalines made by the process.

7 Chii'ns, No Drawings PREPARATION OF ssuasrIIUTED'f I Z-HYDROXYQUINOXALINES BY REACTION or O-ARYLENEDIAMINES WITH TRIHALOVINYL EPOXIDES CROSS-REFERENCE TO RELATED APPLICATION This is a division of my copending application, Ser. No. I58,520, filed June 30, 1971 now abandoned.

BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to novel Z-hydroxy-S-perfluoroalkylquinoxalines and the preparation of these and other 3-substituted Z-hydroxyquinoxalines by reaction of o-arylenediamines with trihalovinyl epoxides 2. Prior Art Z-Hydroxyquinoxalines and their tautomeric 2-oxol,2-dihydroquinoxalines are known to be obtainable by the reaction of o-phenylenediamines with a-oxo carboxylic acids, e.g., gloxylic and pyruvic acids. This specific reaction is one of a number of variations of the well-known I-Iinsberg reactionof o-diamines with 1,2- dicarbonyl compounds (Richters) "Organic- Chemistry", 12th Ed., Vol. IV, I947, pp. 300-303; Karrer, Organic Chemistry", 4th Ed., I950, p. 459; Rodd, Chemistry of Carbon Compounds", Vol. III-A (I954), pp. 225226, and Vol. IV-B (1959), pp. I345, 1346, 1355,1356).

No 2-hydroxy-3-perfluoroalkylquinoxalines have been found in the literature. The reaction of oarylenediamines with trihalovinyl epoxides has likewise not previously been reported.

DESCRIPTION OF THE INVENTION Process of the Invention A NH X R ii" iii 1 \Z V 2/ 1 MHz X X III wherein R may be hydrogen, fluorine, chlorine, lower perfluoroalkyl or phenyl; R completes a carbocyclic aromatic nucleus of 6 to 10 carbons which may be Details of the Process The reactionof an o-arylenedi'amine with a tri- 5 halovinyl epoxide is readily accomplished by mixing the reactants in an inert solvent medium containing a non-nucleophilic base, at a temperature in the range from about to. about I20C.

Conveniently, increments of the epoxide are added to a solution of'the diamine and base in the solvent medium. The order and method of mixing the reactants are not, however, critical and can be arranged in any suitable fashion which allows for control of the reaction temperature within the above-stated range.

The proportions of the essential components of the reaction mixture are not critical. The diamine and epoxide reactants are ordinarily used in about equivalent proportions since no advantage is obtained by using either in excess. The specific role of the base is not known, and it has been found useful in any proportion within the range of about 0.l to 10 moles per mole of diamine or epoxide. The amount of solvent medium used is dependent upon the temperature of reaction .andthe solubility of the diamine reactant, and is ordi- 'narily at least a sufficient amount to completely dissolve the diamine at the lowest temperature employed.

Any commonly inert organic solvent which readily dissolves the diamine reactant may be used. Such solvents include aliphatic and aromatic hydrocarbons, halohydrocarbons, nitriles and ethers. Aliphatic ethers such as diethyl ether, glycol dimethyl ether, tetrahydrofuran and dioxane are preferred solvents.

' 'o-Arylenediamines and trihalovinyl epoxides are generally operable in the process, the only qualification being that compatible substituents present in either reactant age preferably not competitively reactive with any compbnent of the other. Formulas II and Ill given abovefor diamine and epoxide reactants represent reasonably accessible starting materials that can be "used; and formula IV, representing the Z-hydroxyquinoxaline products, includes known compounds which have been obtained in other ways, e.g., by the l-linsbergf'reaction.

Representative Reactants and Products In the followingtable, each horizontal entry shows substituted with one or more common substituents. representative o-afylenediamine and trihalovinyl epoxsuch as halogen, cyano, lower alkyl, lower alkoxy, caride reactants in the first two columns, and -the correboxyl, lower alkoxycarbonyl, hydrocarbon aryl, or hy- Sponding Z-hydroxyquinoxaline products in the third drocarbon aralkyl; and X, X and X individually, are column. All of the listed o-arylenediamines and fluorine or chlorine. trihalovinyl epoxides are known compounds.

TABLE o-Ary|enediamine Trihalovinyl Epoxide mi, I.

o-phenylenediamine Z-Hydroxyquinoxalines 2-hydroxy-3-pentafluoroethylquinoxaline TABLE-continued o-Arylenediamine Trihalovinyl Epoxide Z-Hydroxyquinoxalines "Ion on 11, ""2 N r Ir ocn OCH 7 en 3 CF, CFCI 3 2,3-diamino-4- chlorotrifluoroethy- 3-fluoro-2-hydroxy- S-fluoro-Z-hydrox -8- methoxytoluene lene oxide S-methoxy-S-methylmethoxy -S-methy quinoxaline quinoxallne l2. NC- 0 N on on (an, (5C1 E): I

CF, CHF 3,4-diaminobenzotrifluoroethylene Z-hydroxyquinoxaline- 2-h droxyqumoxaline-finitrile oxide T-carbonitrile car onitnle WT MI NH r c F i E F 2 CF, cF-cm, 4-phenylo-phenylperfluoro l -hexene 2-hydroxy-3-nonafluoro- Z-hydroxyJ-nonaenediamine epoxide butyl-7-phenylquinoxaline fluorobutyl-6- phenylquinoxaline N, on o 144 lC M C-@l::; Q l N CH-@-I (c H ("a"), n

2 2 01,0 CHCl 5 3,4-diaminotriphenyltrichloroethylene- 2-hydroxy-7-(di henyl- 2hydroxy-6-(di henylmethane oxide methyl)quinoxa inc methyl )quinoxa inc EMBODIMENTS OF THE INVENTION The following examples illustrate the process of the invention and describe specific new 2-hydroxy-3-perfluoroalkylquinoxalines.

EXAMPLE 1 2-Hydroxy-3-trifluoromethylquinoxaline NH F (I NR2 &

i H oil;

(A) 2-hydroxy-3- trifouoromethylquinoxaline (B) 2-pentafluoroethylbenzimidazole (C) 2-oxo-3-trifluoromethyl-l, E-dihydroquinoxaline Hexafluoropropylene oxide (19.2 g, 0.] mole) was slowly bubbled into a stirred slurry of o-phenylenediamine (10.8 g, 0.10 mole) and potassium carbonate (5.0 g, 0.036 mole) in ehtyl ether (120 ml) maintained at l5C. After addition was complete, the mixture was stirred at for 18 hours, filtered, and the solid washed with ethyl ether. The combined filtrates were concentrated to give unchanged o-phenylenediamine (4.6 g, 42%) and 2-pentafluoroethylbenzimidazole (2.4 g, l0%). The solid from the filtrationwas extracted exhaustively with warm ethyl ether to give Z-hydroxy- 3-trifluoromethylquinoxaline (4.7 g, 22%), mp. 235.

Spectral data: uv (CF CN); 362 (e 4640), 292 (6 6290), sh 255 (e 3380), 230 nm (e 24,200 PMR N OH [I I (DMSO-d 3.2-3.7 (broad singlet, lH), 7.2-8.1 ppm (aryl mult, 4H). FMR (DMSO); 68.8 ppm (singlet).

( l l Similar results are obtained with telrahydrol'urun as solvent in place of ethyl ether. (2) A and C are in lautomeric equilibrium.

EXAMPLE 2 2-Hydroxy-7-mehtyl-3-trifluor0methylquinoxaline 11 N112 H30 H o CF CFCF3 N112 F3 Into a slurry of 3,4-diaminotoluene (13.4 g, 0.11 mixture was warmed to 25 and filtered. The filtrate mole), potassium carbonate (15.2 g, 0.11 mole), and was concentrated in vacuo and the residue crystallized tetrahydrofuran (150 ml) maintained at was bubfrom ether to give crude 7-ch1oro-2-hydroxy-3-tribled hexafluoropropylene oxide (19.7 g, 0.12 mole). fluoromethylquinoxaline (9.8 g, 36%). This was sub- After standing at for 18 hrs., the mixture was fillimed at 150/0.5 mm to give pure material (8.55 g,

tered and the filtrate concentrated to a volume of 100 31%), -P- r g phy of the residue ml. Ether was added to give 6.0 g of gray crystals, m.p. gave 5-chlore-2-pentafluoroethylbenzimidazole (5.0 g, 248 dec. Concentration of the mother liquor and addi- 16.5%) and 6-chloro-2-hydroxy-3-trif1uoromethyltion of ether was repeated twice to give additional quinoxaline (0.4 g, 1.5%).

crops of 3.8 g and 2.2 g. Sublimation of the combined crude material at 150/0.5 mm gave 10.8 g of off-white Analfor s 2; 22-93; Powder; -P- Yemen Found: 4 335;; 11, 1.54; F. 23.61; Spectral Data 43.49 1.37

IR (KRr): 3000-2800, 1680, 1160, and 1060 cm 11-" PMR (DMSO-d 6 2.43 (singlet, 311), 7.1-7.9 ppm (mult., 3H)

FMR (acetone-d 6 70.5 ppm (singlet) uv c1-1,cN 362 (e, 6000), 297 (e, 7170 25s sh 25 EXAMPLE 4 (e, 2320), 233 (6, 23,200) 2-Hydroxy-3-trifluoromethylbenzo[f]quinoxaline CF CFCF Anal.Ca1ed.fo1-C ,H,F,N,0: C. 52.64; 11.3.09; N. 12.28 35 Hexafluoropropylene oxide (24 g, 0.14 mole) was Found: c. 51.65; 11.2.32; N, 12.35

5197 2.89 122 slowly bubbled into a slurry of 1,2 d1am1nonaphthalene um; (22 g, 0.14 mole), potassium carbonate (9.5 g, 0.069 (1) 3-Hydrmiy-6-methyl-2-1rifluoromethylquinoxaline can also he named (less mole) and [eu-ahyd f 150 ml) at 250 30u. After the addition was complete, the mixture was stirred for 40 an additional 20 minutes, filtered, and the solid washed with tetrahydrofuran. The solid was heated to boiling in EXAMPLE 3 tetrahydrofuran (200 ml), filtered, and the filtrate 7-Chloro-2-hydroxy-3-trifluoromethylquinoxaline cooled to give 2.5 g of product. A second crop of 0.9 g

I c1 1111 (:1 0H

+ CF CF--CF CF N11 H c1 1 F 0P 01 N F3 N H A. 7-chloro-2-hydroxy-3-trifluoromethylqutnoxalme was obtained by concentratmg the mother liquor from B. 6-chloro-Z-hydroxy-3-trifluoromethylquinoxaline the first crop. The mother liquor from the second crop C. 5-ch1oro-2-pentafluoroethylbenzimidazole was combined with the filtrate of the crude reaction Over a period of one hour hexafluoropropylene oxide mixture. This was chromatographed over silica gel with (19.5 g, 0.117 mole) was bubbled into a stirred slurry ether-tetrahydrofuran to give 14.8 g of product. The of 4-chloro-o-phenylenediamine (15.6 g, 0.11 mole) product fractions were combined and recrystallized and potassium carbonate (13 g, 0.095 mole) in tetrahyfrom tetrahydrofuran to give yellow needles, 19.4 g, drofuran ml) maintained at 3.5 to 12. After all of 53%; m.p., 318-22. the hexafluoropropylene oxide had been added. the Spectral Data 9 IR (KBr): 3000, 1680, 1630, 1520, 1180, 1135, and

PMR (DMSO-d 6 7.3-7.8 (aryl mult., 5H). 8.l5-8.4 ppm (mult., 1H) FMR (THF): 68.8 ppm (singlet).

Anal. Calcd. for CuHqFqNgOi C, 59.10: H, 2.67 N, 10.60 Found: C. 58.67; H. 3.17 N, 10.40 58.22 3.03 10.17 58.36 2.99 10.24

EXAMPLE 5 2-Hydroxy-3Trifluoromethylquinoxaline-6-carboxylic Acid N3 U CF CFCF H 0 N11 N F H0 0 3 l-lexafluoropropylene oxide (21.6 g, 0.13 mole) was bubbled into stirred slurry of 3,4-diaminobenzoic acid (18.2 g, 0.12 mole) and potassium carbonate (16 g, 0.12 mole) in tetrahydrofuran (250 ml) maintained below The mixture was stirred at 25 for one hour, filtered, and the solid washed with tetrahydrofuran. The combined filtrates were concentrated and extracted with ehtyl ether, leaving 10.93 g of tan solid. This was recrystallized from hot ehtyl ether containing a small amount of tetrahydrofuran to give 7.7 g of almost colorless crystals, m.p. 318. Spectral Data IR (KBr): 3000-2700 (broad), 1670, 1600, 1400,

1270, 1140,1050 cm PMR (DMSO-d,): 1.61 (broad singlet, 1H), 3.48 (broad singlet, 1H), 7.29 (aryl multeplet, 1H), 8.10 ppm (aryl multiplet, 2H) FMR (DMSO-d 70.8 ppm (singlet) Anal. Calcd. for C H,F,N,O,: C, 46.5 3; H, 1.95; F, 22.08; N, 10.85; Found: C, 48.03; H, 2.57; F, 21.43; N, 9.81;

UTILITY All of the products of formula IV are high boiling and have very high chemical and thermal stability in the molten state. They are therefore useful as heat-transfer media in corrosive atmospheres, e.g., as substitutes for Woods metal in oxidizing or acidic atmospheres which would attack Woods metal.

The use of 2-hydroxy-3trifluoromethylquinoxaline (Example 1 as a bath material for a high-temperature bath is illustrated in:

EXAMPLE A A SO-ml beaker containing 22 g of 2-hydroxy-3-trifluoromethylquinoxaline was heated with a mantle to 240. The clear liquid remained unchanged for 20 minutes. Then a l0-ml flask containing 5.5 ml of tetraglyme (tetraethyleneglycol dimethyl ether; b.p. 252 C.) under a reflux condenser was lowered into the bath.

10 The bath was heated to 255 to maintain the tetraglyme at refluxfor 30 minutes. The bath was cooled to room temperature and a sample removed, m.p. 235-6 (unchanged from before heating).

It should be noted that bath material solid at room temperature is more convenient to handle than an oil. Furthermore, the present organic compounds are less dense than metals often used for high-temperature baths, thereby resulting in a lighter weight bath.

Since obvious modifications and equivalents will be evident to those skilled in the chemical arts, I propose to be bound solely by the appended claims.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A process for preparing a 3-substituted Z-hydroxyquinoxaline which consists essentially of mixing a trihalovinyl epoxide of the formula where R is hydrogen, fluorine, chlorine, lower perfluoroalkyl or phenyl: and the X's, alike or different, are fluorine or chlorine; and

an o-arylenediamine of the formula where R is divalent and completes a carbocyclic aromatic nucleus of 6 or 10 carbons which may be substituted with 1 to 3 of halogen, cyano, lower n-alkyl, lower n-alkoxy, lower n-alkoxycarbonyl, carboxyl, phenyl or phenylalkyl in an inert solvent for the diamine having a non-nucleophilic base at a temperature in the range of 25 to C 2. The process of claim I in which the formula of the diamine is wherein R, R, R and R, individually, may be hydrogen, lower n-alkyl, halogen or carboxyl; and R and R, conjointly, may be divalent 1,4-butadienylene.

3. The process of claim 2 in which hexatluoropropylene oxide and o-phenylenediamine are reacted together.

4. The process of claim 2 in which hexafluoropropylene oxide and 3,4-diaminotoluene are reacted together.

S. The process of claim 1 in which hexafluoropropyltogether. ene oxide and 4-chloro-o-phenylenediamine are re- 7. The process of claim 2 in which hexafluoropropylacted together. ene oxide and 3,4-diaminobenzoic acid are reacted 6. The process of ciaim 2 in which hexafluoropropyi- 5 logeiheli ene oxide and l ,2-diamindnaphlhalene are reacted 

1. A PROCESS FOR PREPARING A 3-SUBSTITUTED 2-HYDROXYQUINOXALINE WHICH CONSISTS ESSENTIALLY OF MIXING A TRIHALOVINYL EPOXIDE OF THE FORMULA
 2. The process of claim 1 in which the formula of the diamine is
 3. The process of claim 2 in which hexafluoropropylene oxide and o-phenylenediamine are reacted together.
 4. The process of claim 2 in which hexafluoropropylene oxide and 3,4-diaminotoluene are reacted together.
 5. The process of claim 2 in which hexafluoropropylene oxide and 4-chloro-o-phenylenediamine are reacted together.
 6. The process of claim 2 in which hexafluoropropylene oxide and 1,2-diaminonaphthalene are reacted together.
 7. The process of claim 2 in which hexafluoropropylene oxide and 3,4-diaminobenzoic acid are reacted together. 